Humans are the longest-lived primates, and are unusually vulnerable to age-related neurodegenerative diseases, including Alzheimer's Disease (AD), which is known to occur only in humans. Despite the importance of understanding normal and pathological patterns of human brain aging, little systematic research has been done to rigorously characterize either the species-specific features of human brain aging or the features humans share with other primates. We propose to take advantage of recent advances in non-invasive imaging technology to compare the time course and regional pattern of brain aging in humans to that of chimpanzees (the animals most closely related to humans) and macaque monkeys. This project will scan the same subjects studied in the other projects in this Program Project Grant, consisting of female macaques, chimpanzees, and humans divided into young adult, middle-aged, old groups, as well has groups of humans with Mild Cognitive Impairment (MCI) and AD. In addition, in a separate group of macaques and chimpanzees, we will validate imaging results by postmortem examination of tissue. The specific aims of this project include: (1) documenting both species-specific and shared patterns of age- and disease-related changes in gray matter and white matter volumes, using T1-weighted magnetic resonance imaging (MRI), and the incidence of white-matter lesions, using T2-weighted and diffusion-tensor imaging (DTI); (2) documenting changes in tissue microstructure using DTI to measure water diffusivity that could reflect changes in neuronal and glial density; (3) validating imaging results regarding tissue volume and microstructure with postmortem histological examination of the scanned tissue.